Graphical Abstract:

Abstract:

Introduction: Addiction is a compulsive drug-seeking and drug-taking behavior. Reduction
of high-risk behaviors can reduce the burden of addiction in society and can improve the overall
prognosis of drug addiction. The aim of this study is to show that reduction of oxidative stress with
socialization will reduce occurrence of high-risk behavior during addiction period.

Method: Fifty-four male Sprague-Dawley rats were randomly divided into four groups: socialized,
isolated, addicted socialized and addicted isolated. For inducing morphine dependence, rats received
morphine (5 mg/rat/kg/day) for 14 days. Socialization was induced by putting two rats in a large cage
for 14 days. On the other hand, isolation was induced by putting rats in separate small cages covered
with black plastic for the same period. At the end of the study, rats were experimented with shuttle
box for assessing avoidance memory and also tested with social interaction test to measure noveltyseeking
behavior and anxiety level. Then, animals were sacrificed for neurochemical analysis. Brain
was isolated to assess oxidative-stress (OS) indices such as malondialdehyde (MDA), glutathione and
nitrite/nitrate in prefrontal cortex and hippocampus.

Results: After 14 days of morphine injection, rats in socialized group had improved avoidance
memory, increased anxiety levels and reduced novelty-seeking behavior. Furthermore, isolated rats
had reduced glutathione and nitrite/nitrate, and higher MDA levels in prefrontal cortex and hippocampus
as compared to socialized rats.

Conclusion: Pair state had positive effect on OS indices in prefrontal cortex and hippocampus and results
in the reduction of relapse and poor prognosis. Thus, OS plays an important role in alleviation of
severity of addiction period.

Abstract:Introduction: Addiction is a compulsive drug-seeking and drug-taking behavior. Reduction
of high-risk behaviors can reduce the burden of addiction in society and can improve the overall
prognosis of drug addiction. The aim of this study is to show that reduction of oxidative stress with
socialization will reduce occurrence of high-risk behavior during addiction period.

Method: Fifty-four male Sprague-Dawley rats were randomly divided into four groups: socialized,
isolated, addicted socialized and addicted isolated. For inducing morphine dependence, rats received
morphine (5 mg/rat/kg/day) for 14 days. Socialization was induced by putting two rats in a large cage
for 14 days. On the other hand, isolation was induced by putting rats in separate small cages covered
with black plastic for the same period. At the end of the study, rats were experimented with shuttle
box for assessing avoidance memory and also tested with social interaction test to measure noveltyseeking
behavior and anxiety level. Then, animals were sacrificed for neurochemical analysis. Brain
was isolated to assess oxidative-stress (OS) indices such as malondialdehyde (MDA), glutathione and
nitrite/nitrate in prefrontal cortex and hippocampus.

Results: After 14 days of morphine injection, rats in socialized group had improved avoidance
memory, increased anxiety levels and reduced novelty-seeking behavior. Furthermore, isolated rats
had reduced glutathione and nitrite/nitrate, and higher MDA levels in prefrontal cortex and hippocampus
as compared to socialized rats.

Conclusion: Pair state had positive effect on OS indices in prefrontal cortex and hippocampus and results
in the reduction of relapse and poor prognosis. Thus, OS plays an important role in alleviation of
severity of addiction period.